Septic Thrombophlebitis

Septic thrombophlebitis is a condition characterized by venous thrombosis, inflammation, and bacteremia or fungemia.[1] The clinical course and severity of septic thrombophlebitis are quite variable. Many cases present as benign, localized venous cords that resolve completely with minimal intervention, however other cases present as severe systemic infections culminating in profound shock that is refractory to aggressive management, including operative intervention and intensive care. 

A number of distinct clinical conditions have been identified, depending on the vessel involved, but all thrombophlebitides involve the same basic pathophysiology. Thrombosis and infection within a vein can occur throughout the body and can involve superficial or deep vessels. Notable examples are thrombophlebitis in the following:

• Peripheral veins

• Pelvic veins

• Portal vein (pylephlebitis)

• Superior vena cava (SVC) or inferior vena cava (IVC)

• Internal jugular vein (Lemierre syndrome)

• Dural sinuses

Sites of septic thombophlebitis are in part explained by Virchow's triad (the conditions leading to thrombus): Venous stasis, hypercoagulability, and inflammation. Some of the more common sites of septic thrombophlebitis are more prone to venous stasis or local inflammation due to adjecent infection are explained by anatomy.[2] The approach to treatment of septic phlebitis depends on which structures are involved, the underlying etiology of the phlebitis, the causative organisms, and the patient's underlying physiology. 

Peripheral septic thrombophlebitis is a common problem that can develop spontaneously but more often is associated with breaks in the skin. Though most commonly caused by indwelling catheters, septic thrombophlebitis may also result from simple procedures such as venipuncture for phlebotomy and intravenous injection. While infection must always be considered, catheter-related phlebitis can result from sterile chemical or mechanical irritation.

Septic phlebitis of a superficial vein without frank purulence is known as simple phlebitis. Simple phlebitis is often benign, but when it is progressive, it can cause serious complications, and even death.

Suppurative superficial thrombophlebitis is a more serious condition that can lead to sepsis and death, even with appropriate aggressive intervention.[3] A frequent complication is embolization of infected thrombus to distant sites, most commonly the lungs, leading to septic pulmonary emboli, hypoxia, sepsis, and often death.[4] Patient factors such as burns,[5] steroid usage,[6] or intravenous drug use[4] increase the risk of developing septic phlebitis and its complications.

Septic phlebitis of the deep venous system is a rare, but life-threatening, emergency that may fail to respond to even the most aggressive therapy. Any vessel can theoretically be involved, but the more common entities are detailed below.

Septic thrombophlebitis of the IVC or SVC is primarily the result of central venous catheter placement, with increased incidence in burn patients and those receiving total parenteral nutrition.[7] Patients are generally very ill appearing with high fever, and they may also have signs of venous occlusion, including arm and neck edema. The mortality rate of these infections is high, but cases of successful treatment have been reported.[7]

Lemierre syndrome is a suppurative thrombophlebitis of the internal jugular vein caused by oropharyngeal infections such as tonsillitis and dental infections. Spread of the infection into the parapharyngeal space that houses the carotid sheath leads to local inflammation and thrombosis of the jugular vein. Lemierre syndrome is easily missed and is more common than is generally appreciated.[8, 9] Unlike superficial vein thrombophlebitis, septic pulmonary emboli are nearly always present and lead to grave complications such as empyema, lung cavitation, and hypoxemia. Less commonly, septic emboli may traverse a patent foramen ovale and cause distant metastatic infections such as septic arthritis, osteomyelitis, and hepatic abscesses.[10]

Septic pelvic thrombophlebitis and ovarian vein thrombophlebitis are seen principally as a complication of puerperal uterine infections, such as endometritis and septic abortion.[11] Rarely, pelvic phlebitis may result from severe pelvic inflammatory disease or progressive infection of the urinary tract. In abdominal infections, such as appendicitis and diverticulitis, infection may spread to cause neighboring septic phlebitides.

Thrombophlebitis of the intracranial venous sinuses is a particularly morbid problem and can involve the cavernous sinus, the lateral sinus, or the superior sagittal sinus. Cavernous sinus thrombophlebitis is caused by infection of the medial third of the face known as the "danger zone," ethmoid and sphenoid sinusitis, and, occasionally, oral infections. Mastoiditis and otitis media are rarely associated with septic phlebitis of the lateral sinuses, while thrombophlebitis of the superior sagittal sinus is the rarest and is primarily associated with meningitis. More than a third of cases of intracranial septic thrombophlebitis are fatal.[12]

Patient education

For patient education information, see Phlebitis.

Causes of peripheral, IVC, and SVC phlebitis include the following:

• Venipuncture

• Central and peripheral catheterization

• Intravenous drug use

• Abrasions and lacerations

• Soft-tissue infection

• Hypercoagulable states

• Burns

Causes of pelvic, ovarian, and pyelophlebitis include the following:

• Diverticulitis

• Endometritis

• Pelvic inflammatory disease

• Septic abortion

• Childbirth

• Appendicitis

• Any intra-abdominal infection

• Cesarean delivery

• Intra-abdominal surgery

• Hypercoagulable states

Causes of Lemierre syndrome include the following:

• Pharyngitis

• Dental infections

• Hypercoagulable states

Causes of dural vein thrombophlebitis include the following:

• Oropharyngeal infection

• Mastoiditis

• Otitis media

• Facial soft-tissue infections

• Meningitis

• Hypercoagulable states

Superficial septic thrombophlebitis

Placement of an intravascular catheter is the main causative factor in the development of phlebitis and septic thrombophlebitis. Infection can be introduced during the placement of the catheter or bacteria can colonize first the hub and then the lumen of the catheter before they gain access to the intravascular space.[13] Once inside the venous system, bacteria can proliferate, causing endothelial damage, local inflammation, and thrombosis.

Causative organisms are diverse and include skin and subcutaneous tissue pathogens, enteric bacteria, and flora causing infection in the genitourinary tract. The most common infective organism is Staphylococcus aureus, but coagulase-negative staphylococci, enteric gram-negative bacilli, and enterococci are also frequently implicated.[14]

Impaired local defense, as well as a heavy burden of skin inoculum, increase burn patients’ susceptibility to thrombophlebitis. These infections are often polymicrobial.[5] Steroid use[6] and injection drug use[4] are other important risk factors.

Deep septic thrombophlebitis

Septic pelvic and ovarian vein thrombophlebitides are often puerperal and typically occur within 3 weeks of delivery.[15] They result from a localized uterine infection, such as endometritis. Damage to the intima of pelvic ileofemoral vessels during vaginal or cesarean delivery is thought to contribute to the process of thrombosis. Hypercoagulability secondary to pregnancy, as well as the venous stasis common in the peripartum state, also contribute.[11] Pathogens responsible for endometritis, such as streptococci, Enterobacteriaceae, and anaerobes, are likely causative, but cultures are often negative.

Septic thrombophlebitis of the portal vein, known as pylephlebitis, is a rare complication of diverticulitis (found to be the inciting infection in 32% of cases). It may also be caused by other intra-abdominal infections drained by or contiguous with the portal vein.[16] Local infection of an adjacent structure can cause extravasation of bacteria and toxin-inducing thrombosis and infection. Bacteroides fragilis is the most common pathogen, but other bacteria, such as Escherichia coli, Klebsiella species, and other Bacteroides species, are also found.[16]

Septic IVC/SVC thrombophlebitis has been found almost exclusively in the setting of central venous catheter placement with the subsequent development of thrombosis, infection, and worsening systemic disease. However, a case report found an IVC filter to be the nidus of a septic phlebitis.[17] In addition to Staphylococcus species, other skin flora and fungal pathogens cause a significant portion of infections. Candida albicans is the most common fungal pathogen, but cases have also been attributed to Candida glabrata.[17]

Lemierre syndrome

Like abdominal and pelvic thrombophlebitis, Lemierre syndrome is characterized by the migration of bacteria through the deep tissues. In this infection, pathogens translocate through the pharynx or are drained from the pharynx into the lateral pharyngeal space, where they come near to the internal jugular vein. Inflammation, thrombosis, and infection may then ensue.[18]

Lemierre syndrome, interestingly, is caused in 80% of patients by Fusobacterium necrophorum,[19] though infections by other pathogens—namely Fusobacterium nucleatum, Bacteroides species, and streptococcal species—have also been reported.[10]

Septic thrombosis of the dural venous sinuses

The predisposing infections that ultimately result in septic thrombosis of the dural venous sinuses are closely related to the venous anatomy of the face and head. Infections of the medial third of the face, involving the nose, periorbital regions, tonsils, and soft palate, have long been recognized risk factors, since these areas drain directly into the cavernous sinus via the facial veins, pterygoid plexus, and ophthalmic veins. Infections of the sphenoid and ethmoid sinuses have been implicated, with bacteria spreading directly through the lateral wall or via emissary veins.[12] Mastoiditis, resulting from chronic ear infections, is almost wholly responsible for cases of septic lateral sinus thrombosis.[12]

While extremely rare, septic thrombophlebitis of the superior sagittal sinus is caused by bacterial meningitis, but frontal, ethmoid, and maxillary sinus infections and spread from infections in the lateral dural sinus have also been reported.[12]

The microbiology of intracranial vascular infections depends in large part on the causative infective site. S aureus is by far the most common organism seen in cavernous sinus thrombosis and is responsible for all septic thromboses resulting from facial and sphenoid sinusitis. Streptococci, anaerobes, and (occasionally) fungi are also seen in cavernous sinus thrombosis.[20, 21]

Organisms responsible for superior sagittal sinus thromboses include those responsible for meningitis, notably S pneumoniae, while pathogens more representative of chronic otitis, such as Proteus, S aureus, E coli, and anaerobes, were found to cause lateral sinus thrombophlebitis.[12]

Catheter-associated phlebitis

Catheter-associated bloodstream infection is a common problem well recognized by the hospital community, and major efforts have been made to combat this problem. In 1990, a French study found that 9.9% of patients with peripheral IVs developed signs of phlebitis, while 1.1% became purulent. Similar rates have been noted for central venous catheters.[22] Current research has shown a rate of 0.5 intravenous device ̶ related bloodstream infections per 1000 intravenous device days for peripheral IV catheters and 2.7 for nontunneled, nonmedicated central venous catheters.[23] Burn patients are at an increased risk, with occurrences of septic thrombophlebitis in 4.2% of these individuals.[5]

Noncatheter septic thrombophlebitis

Given the rarity of pelvic, ovarian, jugular, portal, and dural vein septic thrombophlebitides, epidemiologic data describing their frequency are lacking. In general, however, incidences of these deep vein infections appears to be rising, likely owing in part to the increased use of sophisticated diagnostic imaging. In an epidemiologic survey examining the frequency of septic pelvic thrombophlebitis, an overall incidence of 1:3000 deliveries was found, with cesarean deliveries having an approximately 10-fold increase in incidence over vaginal deliveries.[15]

Lemierre syndrome is also infrequent but is easily missed and likely underdiagnosed. Reports from Europe suggested a rate of 0.8 cases per million per year,[24] though subsequent data pointed to an increase in incidence.[25] Septic thrombophlebitis of the dural sinuses is the most rare, with 96 reported cases in the literature over 44 years.[12]

Age-related demographics

Extremes of age predispose patients to catheter-related septic thrombophlebitis. Bloodstream infections were found to be the cause of as much as 30% of nosocomial infections in neonates with intravenous catheters,[26] with undeveloped host defenses thought to be responsible for this. Vulnerability is also increased in elderly persons, likely secondary to concomitant illnesses and a nonspecific, age-related decline in immunologic function.

Garrison et al reported increased risk for the development of major complications from intravenous catheter placement in patients aged 50 years and older, with an odds ratio of 4.7.[27]

Notable exceptions to the above age-related predispositions are Lemierre syndrome and septic pelvic and ovarian thrombophlebitides: Lemierre disease occurs in healthy, young adults with a mean age of onset of 20 years,[8]  whereas septic pelvic and ovarian thrombophlebitides occur in women of childbearing age.

Septic thrombophlebitis is a relatively rare disease that encompasses an array of clinical entities, so data on mortality rates are scarce. Needless to say, it is a serious and dangerous disease,because the infection takes root in the central or peripheral venous system and can readily progress to sepsis and shock.

Metastatic foci of infection are common, with septic pulmonary emboli, infective endocarditis, septic emboli to the central nervous system, osteomyelitis, septic arthritis, and even arteritis all adding to the morbidity and mortality burden of this disease.[14] In fact, major complications occur in about one third of all patients with catheter-associated peripheral septic phlebitis.[14]

Some entities of deep venous thrombosis carry uniquely high mortality rates, with pylephlebitis portending a mortality rate of 32% in one case series of 19 patients.[16] Thrombophlebitis due to Candida species, as seen with central venous catheters, boasts a 22% death rate.[17]

The death rate remains extremely high for patients with septic thrombophlebitis of the intracranial dural sinuses; septic cavernous sinus thrombosis carries a mortality rate of 30%, whereas 78% of patients with infection of the superior sagittal sinus die even with appropriate antibiotic treatment. Serious complications in survivors include ocular palsies, hemiparesis, blindness, and pituitary insufficiency.[12]

Notably, however, pelvic and jugular thrombophlebitis appear to have become less deadly over the years. Early twentieth century data reported a 50% mortality rate in the setting of pelvic thrombophlebitis, whereas one series following more than 44,000 deliveries demonstrated no major complications and not a single death.[15] Lemierre syndrome was previously reported to have a high incidence of mortality; however, with the advent of antibiotics, a meta-analysis of patients from 1980-2017 found the mortality rate was closer to 4.1%.[28]  

Superficial septic phlebitis most often begins with a localized break in the skin, such as placement of an intravenous catheter, a puncture wound, an insect bite, a phlebotomy attempt, or an intravenous injection. Tenderness and erythema are often apparent at the initial site of infection. The original portal of entry may become less obvious over time, as pain, tenderness, swelling, and redness spread along the entire course of the infected vessel.

Baker et al, in a review of 100 patients with peripheral septic phlebitis, reported that 83% of patients note pain as the presenting complaint. Fever occurred in 44%, swelling in 37%, and spontaneous drainage of pus in 9%.[4] Intravenous drug abusers often have localized areas of cellulitis or even frank abscesses at the sites of injection.

Thrombophlebitis in the deep veins is more insidious and typically presents with isolated fever, particularly in patients with catheter-related disease. Usually, there is no pain or swelling at the site of the central venous catheter. Thrombosis of intra-abdominal vessels may also present with abdominal pain and discomfort.[16] Hepatomegaly and jaundice are other symptoms that may also occur in the setting of pyelophlebitis.

Recent childbirth and recent pelvic surgery are important clues in the diagnosis of pelvic thrombophlebitis. Whereas ovarian vein thrombophlebitis is usually diagnosed within 1 week of delivery, septic thrombophlebitis of the ileofemoral vessels typically is seen later.[15] Fever is frequently present, and the patient may also complain of upper thigh or lower abdominal pain, depending on which vessels are involved.[29]

Lemierre syndrome

Sore throat and fever are clues to the diagnosis of Lemierre syndrome, with both symptoms noted in more than 80% of patients. Other symptoms include swollen or tender neck (52%), vague gastrointestinal complaints (50%), and pleuritic chest pain suggesting embolic phenomena to the lungs (31%).[10]

Dural sinus thrombophlebitis

The vast majority of patients with dural venous sinus thrombophlebitis present with severe headache. Clues in the case of cavernous sinus thrombosis include facial or oropharyngeal infection and visual disturbances signifying cranial nerve involvement. The pain of cavernous sinus thrombosis is typically retroorbital in the region of the ophthalmic and maxillary branches of the fifth cranial nerve, and fever; periorbital swelling may also be noted by some patients.[12]

Since lateral sinus thrombosis is generally a complication of middle ear and mastoid infection, most patients present with prolonged earache and fever. Profound headache becomes the predominant symptom once thrombosis ensues. Nausea and vomiting are other nonspecific findings that can help guide the clinician. Vertigo, diplopia, and photophobia are suggestive clues that sometimes occur. Superior sagittal sinus thrombosis presents as profound and worsening headache in the setting of established bacterial meningitis.[12]

Local signs of phlebitis include the traditional cardinal signs of inflammation: calor, dolor, rubor, and tumor (heat, pain, redness, and swelling). Simple phlebitis may produce a painful cord, blanching erythema, and streaking along the venous channel. Septic thrombophlebitis presents with the same symptoms plus fever.[30]

According to Baker et al, in a review of 100 patients with peripheral septic phlebitis, fever was found in 63% patients, erythema and edema were seen in 62% of patients, abscess in 43%, a palpable cord in 20%, and lymphadenopathy in 13%.[4] Suppurative phlebitis is recognized when any amount of purulent material can be expressed from within or around the lumen of a vessel.

In contrast, central line–associated deep vein phlebitis is often clinically occult, because the infected thrombus is located in the region of the catheter tip. Occasionally, erythema, purulence, or surrounding cellulitis at the insertion site is present and should alert the clinician to the possibility of septic thrombophlebitis in the deep vein.[7] If deep system blood flow is obstructed, extremity pain and edema may develop. Verghese et al reported a small series in which 66% of patients with central venous occlusion had corresponding extremity swelling.[7]

Nonspecific findings in pelvic phlebitis, ovarian phlebitis, and pyelophlebitis include fever, abdominal tenderness, and vomiting. Patients often appear clinically ill, with sepsis sometimes apparent on presentation. Helpful, but less common, findings of pyelophlebitis include hepatomegaly and jaundice,[16] whereas cervical motion tenderness and purulent cervical discharge are often discovered in patients with pelvic and ovarian vein disease.

Lemierre syndrome

Early clinical findings in Lemierre syndrome are indistinguishable from pharyngitis, consisting of fever and oropharyngeal pain. An exudative tonsillitis is common, but not invariably present, with pharyngeal pseudomembranes and ulceration occasionally noted. A high degree of clinical suspicion is required, as some patients present with no pharyngeal findings at all.

Tenderness, swelling, and pain over the angle of the jaw are extremely helpful, but they present in only about 52% of patients.[10]

In fact, many patients may present with clinical signs indicative of metastatic disease, such as septic pulmonary emboli with hypoxemia and hemodynamic instability. Findings of septic arthritis and distant soft-tissue infections are also not uncommon.[8] Late in the disease, symptoms progress to severe prostration with respiratory distress.

Sinus thrombophlebitis

The physical findings of thrombophlebitis of the dural sinuses can be specific to the particular sinus involved. Cavernous sinus pathology results in fever in 94% of patients; the triad of ptosis, proptosis, and chemosis in 95% of patients; extraocular movement palsies in 88% of patients; and abnormal fundi in 65% of patients. Other notable signs are lethargy; abnormal ear, nose, and throat (ENT) examination findings; and nuchal rigidity.[12]

An abnormal ear examination, such as posterior auricular swelling and tenderness, purulence from a ruptured tympanic membrane (TM), or a dull, erythematous TM, was noted in 98% of patients with lateral sinus thrombosis. Sixty-five percent of patients with sagittal sinus septic thrombophlebitis present with altered mental status, while 61% have motor deficits.[12]

General laboratory studies

The following studies can be performed:

• Complete blood count (CBC) - Should be sent for evidence of leukocytosis

• Chemistries - Should be sent for evidence of acidosis and electrolyte imbalance in severe infection

• Hepatologies - Should be sent if pylephlebitis is suspected

• International normalized ratio (INR/prothrombin time (PTT)- Useful in case anticoagulation is indicated

Culture

All febrile patients with suspected septic phlebitis should have blood cultures drawn. In cases of catheter-associated thrombophlebitis, cultures from peripheral and central sites should be sent for comparison. Specifically, the diagnosis of catheter-associated deep septic phlebitis is often aided by tip culture. However, the catheter should not be withdrawn in the emergency department (ED) when there is suspicion of thrombus attachment.

Evident purulent material from peripheral soft-tissue sites should be sent for Gram stain and culture. Cervical cultures and pharyngeal cultures should be sent when applicable.

Cerebrospinal fluid (CSF) culture should be sent in the context of suspected meningitis and dural vein thrombophlebitis.

CT scanning with contrast

Contrast-enhanced computed tomography (CT) scanning is generally accepted as the test of choice for most septic thrombophlebitides and should, at minimum, demonstrate a filling defect within the involved vessel. In the context of positive blood cultures, this finding clinches the diagnosis.[31]

CT scanning is particularly useful in the evaluation of portal, pelvic, and internal jugular vein thrombophlebitis,[32] as it may also demonstrate the inciting inflammatory process.

Thrombi with surrounding inflammatory changes are noted on CT scans in cases of septic thrombophlebitis in the superior and inferior vena cava.[33]

Data show detection rates comparable to magnetic resonance (MR) venography for multidetector-row CT angiography in the diagnosis of all types of dural sinus thrombosis.[34]

MRI

Though less data on the efficacy of magnetic resonance imaging (MRI) exist, it is generally accepted as a useful diagnostic modality for most septic thrombophlebitides.

Intra-abdominal thrombophlebitides are well visualized with MRI and show intraluminal thrombus and abnormal thickening and enhancement of the affected vessel's wall.[35, 36]

MR with MR venography is considered the most sensitive noninvasive modality for the imaging of the dural sinuses.[34]

Ultrasonography

Ultrasonography can show venous thrombus and is diagnostic of thrombophlebitis in the setting of positive blood cultures.[37] Ultrasound may also be helpful on the rare occasions of frank abscess in the adjacent tissues.

Since the internal jugular vein is easily accessible, sonography is often helpful in the diagnosis of Lemierre disease.[8]

Periportal collaterals, aeroportia, and liver abscesses may be identified by ultrasonography in the setting of pyelophlebitis.[32]

Ultrasonography was found to be inadequate for septic pelvic thrombophlebitis[35] and cannot be used for the diagnosis of dural vein thromboses owing to poor wave penetration though bone.

Angiography

Angiography can be helpful in the diagnosis of catheter-related thrombophlebitis because it will demonstrate the fibrin sheath adhered to the catheter tip.

Given the rarity of septic thrombophlebitis, as well as the wide variety of vessels involved and the substantial morbidity and mortality, a very high index of suspicion should be maintained by the ED physician.

Prehospital Care

No specific prehospital care is required for septic thrombophlebitis.

Peripheral septic thrombophlebitis

Peripheral intravenous catheters should be removed at the first sign of erythema, induration, or edema.[4] The temptation to try to preserve a peripheral intravenous catheter must be resisted, because complications associated with septic phlebitis are substantial and increase dramatically over time if the catheter is left in place.

Once phlebitis has become suppurative, simply removing the cannula is no longer sufficient. Broad-spectrum antibiotics to cover S aureus, streptococci, and Enterobacteriaceae should be administered. Vancomycin may be used to cover community- and hospital-acquired methicillin-resistant S aureus (MRSA), as well as methicillin-sensitive S aureus (MSSA), and streptococci. Ceftriaxone is a good agent to add for its activity against Enterobacteriaceae, although other cephalosporins are also useful. Remember that polymicrobial infections are especially common in burn patients, and antibiotic treatment should be accordingly broad spectrum. Duration of intravenous therapy can be as short as 7 days, although courses tend to be longer, with the median from one sample of 19.5 days. Oral antibiotics should follow.[38]

Associated abscesses should be incised and drained, and surgical resection of the involved vein and its emissaries is definitive treatment when antibiotics alone have proven insufficient. Larger veins, such as the femoral vein, are more difficult or impossible to excise and are treated conservatively with IV antibiotics, like the pelvic veins.[39]

The role of anticoagulation is uncertain and should not be routinely used unless extension of thrombus is evident.

SVC and IVC septic thrombophlebitis

These deep venous infections are almost always the result of central venous catheterization. In contrast to peripheral venous catheters, infected central venous cannulas should not be removed immediately. Infected and thrombosed central catheters often have an extensive, infected, free-floating fibrin sheath, and a large mass of septic thrombus may be attached to the catheter. If the catheter is withdrawn precipitously, this septic material may embolize to cause infarct and distant septic metastases. Fibrinolysis is sometimes necessary before safe removal can be undertaken.

Broad-spectrum antibiotics are indicated for at least 3-4 weeks. S aureus, followed by streptococci and Enterobacteriaceae, are again the most common organisms, and good empiric antimicrobial choices include vancomycin for gram-positive coverage and a fourth-generation cephalosporin, carbapenem, beta-lactam/beta-lactamase combination, with or without an aminoglycoside, for gram-negative coverage.[1] Coverage for Pseudomonas aeruginosa should be added in patients who are neutropenic or who have severe sepsis.[1] Further antibiotic treatment should be guided by blood culture and sensitivity results. Fungal bacteremia is more common in central catheter–associated thrombophlebitis, particularly in patients receiving total parenteral nutrition (TPN), and can usually be covered by the addition of intravenous fluconazole.

Anticoagulation is often favored in deep vein disease, although no controlled studies have been performed to date. Studies of central venous thrombophlebitis report success with streptokinase, heparin, and enoxaparin.[40]

Internal jugular thrombophlebitis

In the case of Lemierre syndrome, particular attention should be paid to covering anaerobic infections especially F necrophorum, as well as streptococci and Bacteroides species. Empiric antibiotic therapy should include a beta-lactamase–resistant B-lactam to cover F necrophorum since penicillin failure has been reported.[41] Ampicillin-sulbactam, piperacillin-tazobactam, or a carbapenem are all good choices. Duration of intravenous therapy is prolonged, for a duration of at least 3-4 weeks.

The role of anticoagulation in infected jugular vein thrombosis is controversial.[12] Catheter-directed thrombolysis may be an option.[42]

Incision and drainage of adjacent peritonsillar abscess should be performed promptly by an otolaryngological surgeon or trained ED specialist.[10] Surgical resection of infected thrombus is generally reserved in case conservative management fails.

Portal, pelvic, and other intra-abdominal thrombophlebitides

Antibiotic selection for intra-abdominal septic thrombosis requires coverage of Gram-negative organisms and anaerobes. The disease course of septic pelvic thrombophlebitis is improved with anticoagulation,[43] although there is no proven benefit in pylephlebitis. Surgical thrombectomies are again typically reserved for cases that fail conservative management.

Dural sinus thrombophlebitides

Broad antibiotic coverage must be implemented as soon as possible given the devastating outcomes in this disease. The majority of infections are, in fact, due to S aureus,[20, 21] and coverage of MRSA should be routinely instituted in dural sinus phlebitis. Vancomycin is a good initial choice, though rifampin might be added to increased cerebrospinal fluid penetrance. Streptococci and anaerobes should also be covered, particularly in the setting of associated sinus, dental, or ear infection, with the addition of a third- or fourth-generation cephalosporin (ceftriaxone or cefepime) plus an agent like metronidazole for anaerobic coverage. Duration of antimicrobial therapy for all central venous disease is usually 4-6 weeks.

The role of anticoagulation in septic dural vein thrombosis remains controversial.

Surgical/vascular

Well-localized superficial phlebitis, even if suppurative, does not routinely require any consultation. However, patients with widespread suppurative phlebitis or suppurative phlebitis threatening the deep venous system may benefit from consultation with a vascular surgeon. Additionally, the expertise of a general surgeon, gynecologist, otorhinolaryngologist, or neurosurgeon may be indicated, depending on the patient’s focus of infection.

Interventional radiology

Patients with thrombosed and infected central lines can benefit from fibrinolysis prior to removal of the catheter, and consultation with an interventional radiologist may be indicated, although this is often done in an inpatient setting.

Infectious disease

Consultation with an infectious disease specialist may be prudent, particularly when dealing with immunocompromised patients.

Intensive care

Intensive care unit (ICU) consultation is required when clinically warranted.

Outpatient care should be determined on discharge by the admitting team and may include oral antibiotics. Surveillance for endocarditis and recurrent septic phlebitis should be implemented, since these secondary outcomes are not uncommon.

Deterrence and prevention measures include the following:

• Minimize intravenous catheter placement and phlebotomy[3]

• Remove all indwelling catheters promptly[3]

• Implement sterile technique when catheter placement is required[3, 5]

• Favor peripheral cannulization over central cannulization

• Avoid lower limb cannulization when possible

Antibiotics initially are chosen empirically and should be based on the location of the infected thrombus as detailed above. Broad coverage is generally warranted until blood cultures taken from the suppurative vessel have results, at which point deescalation of microbial coverage is appropriate. Because many infections are caused by S aureus, coverage of MRSA should routinely be administered in most cases on initial patient presentation.

Anticoagulation can be considered based on the location of the infected thrombus, and localized fibrinolysis may be warranted in the case of central catheter–associated disease.

Class Summary

Antibiotics are initially chosen empirically and should be based on the location of the infected thrombus as detailed above. Broad coverage is generally warranted until blood cultures taken from the suppurative vessel have results, at which point deescalation of microbial coverage is appropriate. Because many infections are caused by S aureus, coverage of MRSA should routinely be administered in most cases on initial patient presentation.

Vancomycin

Vancomycin is an antibiotic directed against gram-positive organisms and active against Enterococcus species as well as community-acquired and hospital-acquired MRSA.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin with broad-spectrum, gram-negative activity. It has less gram-positive coverage than earlier-generation cephalosporins. It is bactericidal and inhibits cell wall synthesis by binding to penicillin-binding proteins.

Cefepime (Maxipime)

Cefepime is a fourth-generation cephalosporin with coverage similar to ceftriaxone, with the added benefit of pseudomonal coverage.

Clindamycin (Cleocin)

Clindamycin is a lincosamide used for the treatment of serious skin and soft-tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). Clindamycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl transfer ribonucleic acid (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest.

Ampicillin-sulbactam (Unasyn)

Ampicillin-sulbactam is ampicillin plus a beta-lactamase inhibitor. It interferes with cell wall synthesis during active replication, causing bactericidal activity. It covers skin, enteric flora, and anaerobes.

Piperacillin and tazobactam sodium (Zosyn)

This is an antipseudomonal penicillin plus a beta-lactamase inhibitor. It inhibits the biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication.

Imipenem-cilastatin (Primaxin)

Imipenem is a carbapenem. It inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. Cilastatin prevents renal metabolism. It has excellent gram-negative (including pseudomonal) and anaerobic coverage.

Metronidazole (Flagyl)

Metronidazole is an imidazole ring-based antibiotic that is particularly active against various anaerobic bacteria and protozoa.

Fluconazole (Diflucan)

Fluconazole is a selective inhibitor of fungal cytochrome P-450 dependent enzyme. It has fungistatic activity against many candidal species.

Amphotericin B liposomal (AmBisome)

Amphotericin B, which is produced by a strain of Streptomyces nodosus, can be fungistatic or fungicidal (effective against candidal phlebitis). It binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death.

Class Summary

The goal of fibrinolytic therapy is to dissolve an infected fibrin sheath or an infected thrombus that can serve as a nidus for resistant infection and as a source of septic emboli. Catheter-directed local infusions of fibrinolytic agents are safer than systemic fibrinolytic regimens because they use a low dose of the drug and usually do not produce a systemic lytic state. Several fibrinolytic agents are available for local-regional lysis of infected thrombus.

Reteplase (Retavase)

Reteplase is a second-generation recombinant tissue-type plasminogen activator. As a fibrinolytic agent, it seems to work faster than its forerunner, alteplase, and also may be more effective in patients with larger clot burden. In addition, reteplase has been reported to be more effective than other agents in the lysis of older clots. In patients being treated for peripheral vascular disease, reteplase has been reported to cause fewer bleeding complications than alteplase.

Alteplase (Activase)

Alteplase was the first recombinant tissue plasminogen activator to be released for clinical use; it is the agent with which EDs are most familiar.

Although alteplase is best known as a fibrinolytic agent used for coronary artery occlusion and pulmonary embolism, it is also widely used for catheter-directed lysis of deep venous thrombosis, for dissolution of catheter-related thrombus, and for reopening of occluded central lines and thrombosed dialysis grafts.

Class Summary

Anticoagulation with some form of heparin is essential in patients with septic phlebitis, but anticoagulation alone does not guarantee a successful outcome. Progression of the disease may occur despite full and effective heparin anticoagulation. Warfarin should not be used in the acute treatment of septic phlebitis, because the early risk of increased thrombogenesis outweighs any convenience of oral therapy.

Heparin

Heparin is an indirect thrombin inhibitor that complexes with antithrombin to slow or prevent the progression of venous thrombosis. Heparin does not dissolve existing clots. When unfractionated heparin is used, an aPTT of at least 1.5-times the control value is necessary for a therapeutic effect.

Enoxaparin (Lovenox)

Enoxaparin was the first LMWH released in United States and is FDA approved for both the treatment and the prophylaxis of deep venous thrombosis. Enoxaparin is widely used in pregnancy, although clinical trials are not yet available to demonstrate that it is as safe as unfractionated heparin. There is no utility in checking the aPTT; enoxaparin has a wide therapeutic window and the aPTT does not correlate with the anticoagulant effect.